Chest
Volume 121, Issue 5, Supplement, May 2002, Pages 160S-165S
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Inflammation of the Airways and Lung Parenchyma in COPD: Role of T Cells

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A smoking-induced inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, has long been accepted to be the major cause of COPD in smokers. Recent reports have underlined the role of the T lymphocyte as a potentially important factor in the inflammatory process leading to COPD. It has been found that, in the airways and the lung parenchyma, the presence of T cells, predominantly CD8+ T cells, can distinguish between smokers with and without COPD. In addition to T cells, other inflammatory cell types such as neutrophils and macrophages are probably essential in the initial inflammatory process leading to the breakdown of lung tissue, perhaps producing peptides eventually recognized by T cells as antigenic. This would provide an explanation for the T-cell inflammation. Once activated, T cells are present in the lung, and their effector functions would include the attraction and enhancement of the inflammatory function in other inflammatory cells like neutrophils and macrophages. It seems likely that, only when all inflammatory cell types (ie, CD4+, CD8+, neutrophils, and macrophages) are present in the lung, the airways remodeling and parenchymal destruction characteristic of COPD will ensue. If T cells are responsible for the lung injury and progression of COPD, it would resemble a response to an antigenic stimulus originating in the lung. If that were the case, COPD could be considered to be an autoimmune disease triggered by smoking.

Section snippets

The Cellular Inflammatory Infiltrate in the Airways

The earliest, and constant pathological abnormality in the airway of smokers is the cellular inflammatory infiltrate throughout the wall. Inflammation per se may be responsible for mild airflow limitation.7,8,9 Indeed, it has been suggested that inflammation may lead to functional bronchiolar constriction by releasing mediators that may act directly on bronchiolar smooth muscle.10 The chronicity of inflammation would, in turn, produce other changes such as airways fibrosis, and may increase the

Biochemical Markers of Early Lung Inflammation in Smokers

Despite its nonspecific nature, the early inflammatory response to cigarette smoke is probably crucial to the development of subsequent tissue damage and disease in susceptible individuals. Neutrophils and macrophages can potentially produce large quantities of proteases, of which the various elastase enzymes have attracted the most attention as likely causes of loss of elastic recoil and the destruction of the elastic fibers in the lung parenchyma. Indeed, lung specimens from patients with

Differences in Airway Inflammation Between Smokers With and Without COPD

It is reasonable to hypothesize that the inflammatory process in the airways of smokers destined to develop COPD differs from that in individuals who are resistant to the effects of cigarette smoke. This has proved to be difficult to demonstrate, and it remains unclear whether quantitative or qualitative differences in the inflammatory response account for the development of COPD in susceptible subjects. A logical cell to consider first was the neutrophil, which is characteristically present in

Potential Role of the T cells in COPD

The findings of increased numbers of T lymphocytes and especially CD8+ T cells only in lung specimens of smokers who develop COPD is intriguing and supports the notion that tissue injury is dependent on T-cell activity. If so, progress in understanding the transition from lung inflammation to COPD in smokers will depend on an improved understanding of the factors that favor the proliferation of T cells in the lungs, which is an immunologic response.

Based on the known physiologic behavior of T

CD8+ T-Cell Inflammation in Emphysematous Lungs

One of the important consequences of the effector functions of cytotoxic CD8+ T cells is the apoptosis of target cells, and it would not be surprising that apoptosis plays a role in the destruction of lung tissue in patients with emphysema. Majo et al47 have reported that, in smokers with emphysema, both the degree of apoptosis and the number of CD8+ T cells in the alveolar wall increased in parallel with the amount of smoke inhaled (Fig 3). This suggests that the proliferation of cytotoxic T

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